Practical challenges of continuous real-time functional magnetic resonance imaging neurofeedback with multiband accelerated echo-planar imaging and short repetition times.

Continuous real-time functional magnetic resonance imaging (fMRI) neurofeedback is gaining increasing scientific attention in clinical neuroscience and may benefit from the short repetition times of modern multiband echoplanar imaging sequences. However, minimizing feedback delay can result in technical challenges. Here, we report a technical problem we experienced during continuous fMRI neurofeedback with multiband echoplanar imaging and short repetition times. We identify the possible origins of this problem, describe our current interim solution and provide openly available workflows and code to other researchers in case they wish to use a similar approach.

Cortical Bone Mechanical Assessment via Free Water Relaxometry at 3 T.

BACKGROUND: Investigation of cortical bone using magnetic resonance imaging is a developing field, which uses short/ultrashort echo time (TE) pulse sequences to quantify bone water content and to obtain indirect information about bone microstructure. PURPOSE: To improve the accuracy of the previously proposed technique of free water T1 quantification and to seek the relationship between cortical bone free water T1 and its mechanical competence. STUDY TYPE: Prospective. SUBJECTS: Twenty samples of bovine tibia bone. FIELD STRENGTH/SEQUENCES: 3.0 T; ultra-fast two-dimensional gradient echo, Radio frequency-spoiled three-dimensional gradient echo. ASSESSMENT: Cortical bone free water T1 was quantified via three different methods: inversion recovery (IR), variable flip angle (VFA), and variable repetition time (VTR). Signal-to-noise ratio was measured by dividing the signal of each segmented sample to background noise. Segmentation was done manually. The effect of noise on T1 quantification was evaluated. Then, the samples were subjected to mechanical compression test to measure the toughness, yield stress, ultimate stress, and Young modulus. STATISTICAL TESTS: All the statistical analysis (Shapiro-Wilk, way analysis of variance, paired t test, Pearson correlation, and Bland-Altman plot) were done using SPSS. RESULTS: Significant difference was found between T1 quantification groups (P < 0.05). Average T1 of each quantification method differed significantly after adding noise (P < 0.05). VFA-T1 values significantly correlated with toughness (r = -0.68, P < 0.05), ultimate stress (r = -0.71, P < 0.05), and yield stress (r = -0.62, P < 0.05). No significant correlation was found between VTR-T1 values and toughness (P = 0.07), ultimate stress (P = 0.47), yield stress (P = 0.30), and Young modulus (P = 0.39). DATA CONCLUSION: Pore water T1 value is associated with bone mechanical competence, and VFA method employing short-TE pulse sequence seems a superior technique to VTR method for this quantification. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: 1.

[Evaluation of Improvement of Tissue Contrast and Reduction of Imaging Time by Shortening TR in Brain T2 FLAIR Using MTC Pulse].

T2 fluid-attenuated inversion recovery (FLAIR) using inversion recovery pulse to suppress cerebrospinal fluid signal needs adequate T1 recovery time after data acquisition, otherwise, the T2-weighted contrast in brain tissue will get lower. Over 10000 ms of repetition time (TR) is recommended for the 1.5 T MR scanner, so it is difficult to shorten the imaging time. We verified whether T2 FLAIR combined with the magnetization transfer contrast (MTC) pulse shows better gray-to-white matter (GM/WM) and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR. Optimal parameters of the MTC pulse were determined with a self-produced phantom, which modeled on cerebral cortical gray and white matters. GM/WM contrasts of the phantom were measured in T2 FLAIR with the MTC pulse while decreasing TR gradually from 10000 ms to 6500 ms. Although GM/WM contrast of the phantom in T2 FLAIR with the MTC pulse gradually decreased as the TR got shortened, the T2 FLAIR with the MTC pulse of 6500 ms of TR still showed 27% higher contrast than the conventional T2 FLAIR (TR 10000 ms). GM/WM contrast in T2 FLAIR with the MTC pulse was improved also in healthy volunteers, but improvement in thalamo-medullary contrast was less than that of cerebral cortico-medullary and putamino-medullary contrasts. It seems to be because thalamus, which is a deep gray matter, shows a higher MTC effect than other gray matters. Thus, it is necessary to note that the tissue contrast might differ between T2 FLAIR with the MTC pulse and the conventional T2 FLAIR. Because general lesions with an elongated T2 value show lower MTC effect compared to the normal brain tissue, a clinical case with thalamic lesion showed that the lesion-to-normal tissue contrast improved in T2 FLAIR with the MTC pulse of 6500 ms of TR. Although it is necessary to note the difference in contrast between some tissues, T2 FLAIR with the MTC pulse improves GM/WM and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR, and it enables to shorten the imaging time.

Patient-specific 3-dimensionally printed models for neurosurgical planning and education.

OBJECTIVE: Advances in 3-dimensional (3D) printing technology permit the rapid creation of detailed anatomical models. Integration of this technology into neurosurgical practice is still in its nascence, however. One potential application is to create models depicting neurosurgical pathology. The goal of this study was to assess the clinical value of patient-specific 3D printed models for neurosurgical planning and education. METHODS: The authors created life-sized, patient-specific models for 4 preoperative cases. Three of the cases involved adults (2 patients with petroclival meningioma and 1 with trigeminal neuralgia) and the remaining case involved a pediatric patient with craniopharyngioma. Models were derived from routine clinical imaging sequences and manufactured using commercially available software and hardware. RESULTS: Life-sized, 3D printed models depicting bony, vascular, and neural pathology relevant to each case were successfully manufactured. A variety of commercially available software and hardware were used to create and print each model from radiological sequences. The models for the adult cases were printed in separate pieces, which had to be painted by hand, and could be disassembled for detailed study, while the model for the pediatric case was printed as a single piece in separate-colored resins and could not be disassembled for study. Two of the models were used for patient education, and all were used for presurgical planning by the surgeon. CONCLUSIONS: Patient-specific 3D printed models are useful to neurosurgical practice. They may be used as a visualization aid for surgeons and patients, or for education of trainees.

Mutual connectivity analysis of resting-state functional MRI data with local models.

Functional connectivity analysis of functional MRI (fMRI) can represent brain networks and reveal insights into interactions amongst different brain regions. However, most connectivity analysis approaches adopted in practice are linear and non-directional. In this paper, we demonstrate the advantage of a data-driven, directed connectivity analysis approach called Mutual Connectivity Analysis using Local Models (MCA-LM) that approximates connectivity by modeling nonlinear dependencies of signal interaction, over more conventionally used approaches, such as Pearson's and partial correlation, Patel's conditional dependence measures, etcetera. We demonstrate on realistic simulations of fMRI data that, at long sampling intervals, i.e. high repetition time (TR) of fMRI signals, MCA-LM performs better than or comparable to correlation-based methods and Patel's measures. However, at fast image acquisition rates corresponding to low TR, MCA-LM significantly outperforms these methods. This insight is particularly useful in the light of recent advances in fast fMRI acquisition techniques. Methods that can capture the complex dynamics of brain activity, such as MCA-LM, should be adopted to extract as much information as possible from the improved representation. Furthermore, MCA-LM works very well for simulations generated at weak neuronal interaction strengths, and simulations modeling inhibitory and excitatory connections as it disentangles the two opposing effects between pairs of regions/voxels. Additionally, we demonstrate that MCA-LM is capable of capturing meaningful directed connectivity on experimental fMRI data. Such results suggest that it introduces sufficient complexity into modeling fMRI time-series interactions that simple, linear approaches cannot, while being data-driven, computationally practical and easy to use. In conclusion, MCA-LM can provide valuable insights towards better understanding brain activity.

Perturbation of longitudinal relaxation rate in rotating frame (PLRF) analysis for quantification of chemical exchange saturation transfer signal in a transient state.

PURPOSE: To develop a novel analytical method for quantification of chemical exchange saturation transfer (CEST) in the transient state. The proposed method aims to reduce the effects of non-chemical-exchange (non-CE) parameters on the CEST signal, emphasizing the effect of chemical exchange. METHODS: The difference in the longitudinal relaxation rate in the rotating frame ( ΔR1ρ) was calculated based on perturbation of the Z-value by R1ρ, and a saturation-pulse-amplitude-compensated exchange-dependent relaxation rate (SPACER) was determined with a high-exchange-rate approximation. In both phantom and human subject experiments, MTRasym (representative of the traditional CEST index), ΔR1ρ, and SPACER were measured, evaluated, and compared by altering the non-CE parameters in a transient-state continuous-wave CEST sequence. RESULTS: In line with the theoretical expectation, our experimental data demonstrate that the effects of the non-CE parameters can be more effectively reduced using the proposed indices (  ΔR1ρ and SPACER) than using the traditional CEST index ( MTRasym). CONCLUSION: The proposed method allows for the chemical exchange weight to be better emphasized in the transient-state CEST signal, which is beneficial, in practice, for quantifying the CEST signal. Magn Reson Med 78:1711-1723, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Variable slice thickness (VAST) EPI for the reduction of susceptibility artifacts in whole-brain GE-EPI at 7 Tesla.

OBJECTIVE: A new technique for 2D gradient-recalled echo echo-planar imaging (GE-EPI) termed 'variable slice thickness' (VAST) is proposed, which reduces signal losses caused by through-slice susceptibility artifacts, while keeping the volume repetition time (TR) manageable. The slice thickness is varied across the brain, with thinner slices being used in the inferior brain regions where signal voids are most severe. MATERIALS AND METHODS: Various axial slice thickness schemes with identical whole-brain coverage were compared to regular EPI, which may either suffer from unfeasibly long TR if appropriately thin slices are used throughout, or signal loss if no counter-measures are taken. Evaluation is based on time-course signal-to-noise (tSNR) maps from resting state data and a statistical group-level region of interest (ROI) analysis on breath-hold fMRI measurements. RESULTS: The inferior brain region signal voids with static B0 inhomogeneities could be markedly reduced with VAST GE-EPI in contrast to regular GE-EPI. ROI-averaged event-related signal changes showed 48% increase in VAST compared to GE-EPI with regular "thick" slices. tSNR measurements proved the comparable signal robustness of VAST in comparison to regular GE-EPI with thin slices. CONCLUSION: A novel acquisition strategy for functional 2D GE-EPI at ultrahigh magnetic field is presented to reduce susceptibility-induced signal voids and keep TR sufficiently short for whole-brain coverage.

Self-gated fat-suppressed cardiac cine MRI.

PURPOSE: To develop a self-gated alternating repetition time balanced steady-state free precession (ATR-SSFP) pulse sequence for fat-suppressed cardiac cine imaging. METHODS: Cardiac gating is computed retrospectively using acquired magnetic resonance self-gating data, enabling cine imaging without the need for electrocardiogram (ECG) gating. Modification of the slice-select rephasing gradients of an ATR-SSFP sequence enables the acquisition of a one-dimensional self-gating readout during the unused short repetition time (TR). Self-gating readouts are acquired during every TR of segmented, breath-held cardiac scans. A template-matching algorithm is designed to compute cardiac trigger points from the self-gating signals, and these trigger points are used for retrospective cine reconstruction. The proposed approach is compared with ECG-gated ATR-SSFP and balanced steady-state free precession in 10 volunteers and five patients. RESULTS: The difference of ECG and self-gating trigger times has a variability of 13 ± 11 ms (mean ± SD). Qualitative reviewer scoring and ranking indicate no statistically significant differences (P > 0.05) between self-gated and ECG-gated ATR-SSFP images. Quantitative blood-myocardial border sharpness is not significantly different among self-gated ATR-SSFP ( 0.61±0.15 mm -1), ECG-gated ATR-SSFP ( 0.61±0.15 mm -1), or conventional ECG-gated balanced steady-state free precession cine MRI ( 0.59±0.15 mm -1). CONCLUSION: The proposed self-gated ATR-SSFP sequence enables fat-suppressed cardiac cine imaging at 1.5 T without the need for ECG gating and without decreasing the imaging efficiency of ATR-SSFP.

Reduced scan time three-dimensional FLAIR using modulated inversion and repetition time.

BACKGROUND: The purpose of this study is to design and evaluate a new reduced scan time three-dimensional (3D) FLuid Attenuated Inversion Recovery (FLAIR) sequence. METHODS: The 3D FLAIR sequence was modified so that the repetition time was modulated in a predetermined smooth manner (3D mFLAIR). Inversion times were adjusted accordingly to maintain cerebrospinal fluid (CSF) suppression. Simulations were performed to determine SNR for gray matter (GM), white matter (WM), and CSF. Fourteen volunteers were imaged using the modified and product sequence. SNR measurements were performed in GM, WM, and CSF. Mean value and the 95% confidence interval ([CI]) were assessed. Scan time for the 3D FLAIR and 3D mFLAIR sequences was measured. RESULTS: There was no statistically significant difference in the SNR measured in GM (P value = 0.5; mean SNR = 42.8 [CI]: 38.2-45.5 versus 42.2 [CI]: 38.3-46.1 for 3D FLAIR and 3D mFLAIR, respectively) and WM (P value = 0.25; mean SNR = 32.1 [CI]: 30.3-33.8 versus 32.9 [CI]: 31.1-34.7). Scan time reduction greater than 30% was achieved for the given parameter set with the 3D mFLAIR sequence. CONCLUSION: Scan time for 3D FLAIR can be effectively reduced by modulating repetition and inversion time in a predetermined manner while maintaining the SNR and CNR of a constant TR sequence.

Combined molecular MRI and immuno-spin-trapping for in vivo detection of free radicals in orthotopic mouse GL261 gliomas.

Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p<0.001) in MR signal intensity or a significant decrease (p<0.001) in T1 relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p<0.0001) in T1 relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin-Gd-DTPA-biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p<0.001) and 3-nitrotyrosine (3-NT) (p<0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model.

Neural correlates of experimentally induced flow experiences.

Flow refers to a positive, activity-associated, subjective experience under conditions of a perceived fit between skills and task demands. Using functional magnetic resonance perfusion imaging, we investigated the neural correlates of flow in a sample of 27 human subjects. Experimentally, in the flow condition participants worked on mental arithmetic tasks at challenging task difficulty which was automatically and continuously adjusted to individuals' skill level. Experimental settings of "boredom" and "overload" served as comparison conditions. The experience of flow was associated with relative increases in neural activity in the left anterior inferior frontal gyrus (IFG) and the left putamen. Relative decreases in neural activity were observed in the medial prefrontal cortex (MPFC) and the amygdala (AMY). Subjective ratings of the flow experience were significantly associated with changes in neural activity in the IFG, AMY, and, with trend towards significance, in the MPFC. We conclude that neural activity changes in these brain regions reflect psychological processes that map on the characteristic features of flow: coding of increased outcome probability (putamen), deeper sense of cognitive control (IFG), decreased self-referential processing (MPFC), and decreased negative arousal (AMY).

Quantification of track-weighted imaging (TWI): characterisation of within-subject reproducibility and between-subject variability.

Recently several novel image contrasts derived from whole-brain fibre tracking-data (tractograms) have been introduced. The novel contrasts of these track-weighted imaging (TWI) methods may provide important information for clinical neuroscience studies. However, before they can be used reliably to generate quantitative measures, it is important to characterise their within-subject reproducibility, and between-subject variability. In this work we compute the within-subject reproducibility (intra-scan, intra-session and inter-session), and between-subject variability of TWI for a number of different TWI contrasts across multiple subjects. The results are used in simple voxel-wise power calculations within illustrative regions of interest to provide guidelines for required sample sizes and observable effect sizes for individual subjects and between groups. It was found that the required sample sizes and observable effect sizes varied considerably between different TWI maps and for different ROIs. For some TWI contrast and ROI combinations, the power calculations yielded clinically practical values. These results provide important information concerning the potential usefulness and sensitivity of TWI maps for individual diagnosis, longitudinal studies and group comparisons, as well as for study designs.

Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.

Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.

No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men.

BACKGROUND & AIMS: Diets high in fructose have been proposed to contribute to nonalcoholic fatty liver disease. We compared the effects of high-fructose and matched glucose intake on hepatic triacylglycerol (TAG) concentration and other liver parameters. DESIGN: In a double-blind study, we randomly assigned 32 healthy but centrally overweight men to groups that received either a high-fructose or high-glucose diet (25% energy). These diets were provided during an initial isocaloric period of 2 weeks, followed by a 6-week washout period, and then again during a hypercaloric 2-week period. The primary outcome measure was hepatic level of TAG, with additional assessments of TAG levels in serum and soleus muscle, hepatic levels of adenosine triphosphate, and systemic and hepatic insulin resistance. RESULTS: During the isocaloric period of the study, both groups had stable body weights and concentrations of TAG in liver, serum, and soleus muscle. The high-fructose diet produced an increase of 22 ± 52 µmol/L in the serum level of uric acid, whereas the high-glucose diet led to a reduction of 23 ± 25 µmol/L (P < .01). The high-fructose diet also produced an increase of 0.8 ± 0.9 in the homeostasis model assessment of insulin resistance, whereas the high-glucose diet produced an increase of only 0.1 ± 0.7 (P = .03). During the hypercaloric period, participants in the high-fructose and high-glucose groups had similar increases in weight (1.0 ± 1.4 vs 0.6 ± 1.0 kg; P = .29) and absolute concentration of TAG in liver (1.70% ± 2.6% vs 2.05% ± 2.9%; P = .73) and serum (0.36 ± 0.75 vs 0.33 ± 0.38 mmol/L; P = .91), and similar results in biochemical assays of liver function. Body weight changes were associated with changes in liver biochemistry and concentration of TAGs. CONCLUSIONS: In the isocaloric period, overweight men who were on a high-fructose or a high-glucose diet did not develop any significant changes in hepatic concentration of TAGs or serum levels of liver enzymes. However, in the hypercaloric period, both high-fructose and high-glucose diets produced significant increases in these parameters without any significant difference between the 2 groups. This indicates an energy-mediated, rather than a specific macronutrient-mediated, effect. Clinical trials.gov no: NCT01050140.

Alterations in brain structure and neurodevelopmental outcome in preterm infants hospitalized in different neonatal intensive care unit environments.

OBJECTIVE: To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology, and brain structure at hospital discharge; and developmental outcomes at 2 years of age. STUDY DESIGN: In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at 2 years of age (n = 86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were: (1) medical factors throughout the hospitalization; (2) neurobehavior; and (3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). RESULTS: At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores (P = .02; ß = -0.52 [CI -0.95, -0.10]). At age 2 years, infants from private rooms had lower language scores (P = .006; ß = -8.3 [CI -14.2, -2.4]) and a trend toward lower motor scores (P = .02; ß = -6.3 [CI -11.7, -0.99]), which persisted after adjustment for potential confounders. CONCLUSION: These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.

Myelin water quantification in multiple sclerosis using short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) imaging.

Background: Myelin water imaging (MWI) is a myelin-specific technique, which has great potential for the assessment of demyelination and remyelination. This study develops a new MWI method, which employs a short repetition time adiabatic inversion recovery (STAIR) technique in combination with a commonly used fast spin echo (FSE) sequence and provides quantification of myelin water (MW) fractions. Method: Whole-brain MWI was performed using the short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) technique on eight healthy volunteers (mean age: 38±14 years, four-males) and seven patients with multiple sclerosis (MS) (mean age: 53.7±8.7 years, two-males) on a 3T clinical magnetic resonance imaging scanner. To facilitate the quantification of apparent myelin water fraction (aMWF), a proton density-weighted FSE was also used during the scans to allow total water imaging. The aMWF measurements of MS lesions and normal-appearing white matter (NAWM) regions in MS patients were compared with those measured in normal white matter (NWM) regions in healthy volunteers. Both the analysis of variance (ANOVA) test and paired comparison were performed for the comparison. Results: The MW in the whole-brain was selectively imaged and quantified using the STAIR-FSE technique in all participants. MS lesions showed much lower signal intensities than NAWM in the STAIR-FSE images. ANOVA analysis revealed a significant difference in the aMWF measurements between the three groups. Moreover, the aMWF measurements in MS lesions were significantly lower than those in both NWM of healthy volunteers and NAWM of MS patients. Lower aMWF measurements in NAWM were also found in comparison with those in NWM. Conclusions: The STAIR-FSE technique is capable of measuring aMWF values for the indirect detection of myelin loss in MS, thus facilitating clinical translation of whole brain MWI and quantification, which show great potential for the detection and evaluation of changes in myelin in the brain of patients with MS for future larger cohort studies.

Short repetition time diffusion-weighted imaging improves visualization of prostate cancer.

PURPOSE: This study aimed to assess whether short repetition time (TR) diffusion-weighted imaging (DWI) could improve diffusion contrast in patients with prostate cancer (PCa) compared with long TR (conventional) reference standard DWI. MATERIALS AND METHODS: Our Institutional Review Board approved this retrospective study and waived the need for informed consent. Twenty-five patients with suspected PCa underwent multiparametric magnetic resonance imaging (mp-MRI) using a 3.0-T system. DWI was performed with TR of 1850 ms (short) and 6000 ms (long) with b-values of 0, 1000, and 2000s/mm2. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), visual score, apparent diffusion coefficient (ADC), and diagnostic performance were compared between short and long TR DWI for both b-values. The statistical tests included paired t-test for SNR and CNR; Wilcoxon signed-rank test for VA; Pearson's correlation and Bland-Altman plot analysis for ADC; and McNemar test and receiver operating characteristic analysis and Delong test for diagnostic performance. RESULTS: Regarding b1000, CNR and visual score were significantly higher in short TR compared with long TR (P = .003 and P = .002, respectively), without significant difference in SNR (P = .21). Considering b2000, there was no significant difference in visual score between short and long TR (P = .07). However, SNR and CNR in long TR were higher (P = .01 and P = .04, respectively). ADC showed significant correlations, without apparent bias for ADC between short and long TR for both b-values. For diagnostic performance of DWI between short and long TR for both b-values, one out of five readers noted a significant difference, with the short TR for both b-values demonstrating superior performance. CONCLUSIONS: Our data showed that the short TR DWI1000 may provide better image quality than did the long TR DWI1000 and may improve visualization and diagnostic performance of PCa for readers.

Diffusion restriction in the human spinal cord characterized in vivo with high b-value STEAM diffusion imaging.

Restricted or hindered motion of water across axonal membranes as characterized with diffusion-weighted (DW) imaging may be a potential marker of axonal damage in white matter (WM) injury due to trauma, neurodegeneration, or other causes. This study sought to determine whether high b-value DW imaging with a stimulated echo (STEAM) sequence could improve the spatially resolved assessment of tissue architecture in the human spinal cord in vivo. Diffusion times from 76 ms to 1000 ms and b-values of up to 14,750 s/mm(2) were used to acquire axial DW images in six healthy volunteers, and four additional healthy volunteers were studied with a protocol focused on high b-value, higher-resolution imaging. Mono-exponential, diffusional kurtosis, and mono-exponential with an additive constant (MEC) models were fit individually to diffusion decay curves obtained at different diffusion times. Diffusion restriction, characterized with the diffusional kurtosis and MEC models, was measured more precisely using higher b-value ranges. DW images at high b-value and fitting parameters using the large range of b-values available at the diffusion time of 1000 ms demonstrated signal and restriction differences between gray and white matter and even across white matter regions. These white matter differences may reflect variations in axonal density, diameter, or alignment. We conclude that high b-value DW imaging with a STEAM sequence on a conventional clinical scanner can provide accurate measures of diffusion hindrance and restriction in human spinal cord in vivo.

On the use of Cramér-Rao minimum variance bounds for the design of magnetic resonance spectroscopy experiments.

Localized Magnetic Resonance Spectroscopy (MRS) is in widespread use for clinical brain research. Standard acquisition sequences to obtain one-dimensional spectra suffer from substantial overlap of spectral contributions from many metabolites. Therefore, specially tuned editing sequences or two-dimensional acquisition schemes are applied to extend the information content. Tuning specific acquisition parameters allows to make the sequences more efficient or more specific for certain target metabolites. Cramér-Rao bounds have been used in other fields for optimization of experiments and are now shown to be very useful as design criteria for localized MRS sequence optimization. The principle is illustrated for one- and two-dimensional MRS, in particular the 2D separation experiment, where the usual restriction to equidistant echo time spacings and equal acquisition times per echo time can be abolished. Particular emphasis is placed on optimizing experiments for quantification of GABA and glutamate. The basic principles are verified by Monte Carlo simulations and in vivo for repeated acquisitions of generalized two-dimensional separation brain spectra obtained from healthy subjects and expanded by bootstrapping for better definition of the quantification uncertainties.

Relationship between excitability, plasticity and thickness of the motor cortex in older adults.

The relationship between brain structure, cortical physiology, and learning ability in older adults is of particular interest in understanding mechanisms of age-related cognitive decline. Only a few studies addressed this issue so far, yielding mixed results. Here, we used comprehensive multiple regression analyses to investigate associations between brain structure on the one hand, i.e., cortical thickness (CT), fractional anisotropy (FA) of the pyramidal tract and individual coil-to-cortex distance, and cortical physiology on the other hand, i.e. motor cortex excitability and long-term potentiation (LTP)-like cortical plasticity, in healthy older adults (mean age 64 years, 14 women). Additional exploratory analyses assessed correlations between cortical physiology and learning ability in the verbal domain. In the regression models, we found that cortical excitability could be best predicted by CT of the hand knob of the primary motor cortex (CT-M1HAND) and individual coil-to-cortex distance, while LTP-like cortical plasticity was predicted by CT-M1HAND and FA of the pyramidal tract. Exploratory analyses revealed a significant inverse correlation between cortical excitability and learning ability. In conclusion, higher cortical excitability was associated with lower CT and lower learning ability in a cohort of healthy older adults, in line with previous reports of increased cortical excitability in patients with cortical atrophy and cognitive deficits due to Alzheimer's Disease. Cortical excitability may thus be a parameter to identify individuals at risk for cognitive decline and gray matter atrophy, a hypothesis to be explored in future longitudinal studies.