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Biodanza is a new approach towards health and well-being. It aims to work with dance and group experiences to reinforce intra- and inter-individual resources, reduce stress and increase well-being. Up to 2016, 13 studies and one systematic review about Biodanza studies have been published. The Research Network BIONET was created in order to connect researchers and to find a consensus on the standards of good quality studies. In this review, the authors summarised seven Biodanza studies on stress reduction and well-being. The authors describe and create criteria to evaluate the quality of the research works inspired by international standards of clinical and social scientific intervention research. In several studies, Biodanza has an effect on impatience, ability to recover, feeling of activation, physiological sympathetic activity (e.g. heart rate, skin response), increased mood, feeling of well-being, immunological effectiveness on IgA and increased expression of emotion. One study also showed the effect on stress reduction. Also there was a large difference between those who choose Biodanza (they have a significant lower status of stress reduction) and the other groups. In this study, the dropout rate was high (42%); in the other studies, it was under 10%.

The presence of the e4 allele of the apolipoprotein E (APOE) gene is the best-known genetic risk factor for Alzheimer's disease. In this study, we investigated the link between functional and behavioural differences and regional brain volume and cortical thickness differences in those who carry the e4 allele (e4+) and those who only carry the e3 allele (e3/e3). We studied these genotype populations in two age groups: a young group (average age, 21 years) and a mid-age group (average age, 50 years). High-resolution T1 -weighted MRI scans were analysed with Freesurfer to measure regional white matter brain volume and cortical thickness differences between genotype groups at each age. These data were correlated with behavioural findings in the same cohort. Resting-state MRI was also conducted to identify differences in underlying brain functional connectivity. We found that there was a positive correlation between the thickness of the parahippocampal cortex in young e4+ individuals and performance on an episodic memory task. Young e4+ individuals also showed a positive correlation between white matter volume in the left anterior cingulate and performance on a covert attention task. At mid-age, e4+ individuals had structural differences relative to e3/e3 individuals in these areas: the parahippocampal cortex was thicker and white matter volume in the left anterior cingulate was greater than in e3/e3 individuals. We discuss the possibility that an over-engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. The cuneus appears to be an important region for APOE-driven differences in the brain, with greater functional connectivity among young e3/e3 individuals and greater white matter volume in young e4+ individuals. Copyright © 2016 John Wiley & Sons, Ltd.

The evidence-based programme “TANZPRO-Biodanza for children” was developed in 2009 by Marcus Stueck and Alejandra Villegas based on the Biodanza concept of Rolando Toro and Cecilia Luzzi (Children-Biodanza). The 10-session programme includes elements of dance, movement, encounter and non-verbal communication. There are two versions of the programme, for younger children aged 4–6, and older children, aged 7–12. TANZPRO-Biodanza is the nonverbal part of the School of Empathy concept, based on an integrative empathy model by Stueck (2013b, verbal part: “Respectful, nonviolent communication”). In the current study (10 children, age 4–6), a significant reduction in cortisol and improvements in emotion recognition and concentration (in children with high or medium pre-cortisol values) were found. This indicates the potential of TANZPRO-Biodanza to promote stress reduction and the enhancement of social skills. Despite the methodical limitations, the current study is a valid pilot and gives a first insigh...

Present study addresses the question of the effects of the evidence based TANZPRO-Biodanza®-Program (Stueck & Villegas, 2009, Stück, 2013) based on BIODANZA by Rolando Toro and Cecilia Luzzi (Toro, 2010). TANZPRO-Biodanza® is the nonverbal part of the School of Empathy concept by Marcus Stueck (Stueck, 2013), which was developed in the project “Healthy Lifestyles in Kindergardens” of the Geman Ministry of Health (2009 until 2011). Biodanza is a contact and motion-based intervention method with auto-regulative claim on immune competence and the autonomic system of children of kindergarten age. The evaluation took ten weeks. A TANZPRO®-Biodanza class with girls aged four to six was carried out from September 2011 until December 2012. The immunological parameters immunoglobuline A and testosterone as well as the autonomic heart rate parameters were collected before and after each TANZPRO®-Biodanza sessions of the course as a process variable. Especially, the reduced testosterone levels after the meetings in the saliva of children show positive effects of the method on the immune system. The decrease of IgA levels after TANZPRO®-Biodanza in the saliva of children towards age norm might be due to an immune regulative effect. The specific effects of TANZPRO®-Biodanza on heart rate towards a mean level show improvement of physical autoregulatory processes. Key words: auto regulative immune competence, empathy, Immuneglobuline A, TANZPRO®-Biodanza, testosterone.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Over the last few decades there has been considerable research into quantifying the cerebral microvasculature with imaging, for use in studies of the human brain and various pathologies including cerebral tumours. This review highlights key issues in dynamic contrast-enhanced CT, dynamic contrast-enhanced MRI and arterial spin labelling, the various applications of which are considered elsewhere in this special issue of the British Journal of Radiology.

Multicentre imaging studies of brain tumours (and other tumour and brain studies) can enable a large group of patients to be studied, yet they present challenging technical problems. Differences between centres can be characterised, understood and minimised by use of phantoms (test objects) and normal control subjects. Normal white matter forms an excellent standard for some MRI parameters (e.g. diffusion or magnetisation transfer) because the normal biological range is low (2-3%) and the measurements will reflect this, provided the acquisition sequence is controlled. MR phantoms have benefits and they are necessary for some parameters (e.g. tumour volume). Techniques for temperature monitoring and control are given. In a multicentre study or treatment trial, between-centre variation should be minimised. In a cross-sectional study, all groups should be represented at each centre and the effect of centre added as a covariate in the statistical analysis. In a serial study of disease progression or treatment effect, individual patients should receive all of their scans at the same centre; the power is then limited by the within-subject reproducibility. Sources of variation that are generic to any imaging method and analysis parameters include MR sequence mismatch, B(1) errors, CT effective tube potential, region of interest generation and segmentation procedure. Specific tissue parameters are analysed in detail to identify the major sources of variation and the most appropriate phantoms or normal studies. These include dynamic contrast-enhanced and dynamic susceptibility contrast gadolinium imaging, T(1), diffusion, magnetisation transfer, spectroscopy, tumour volume, arterial spin labelling and CT perfusion.

To enhance the reliability and spatial resolution of magnetization transfer ratio (MTR) measurements for interrogation of subcortical brain regions with an automated volume of interest (VOI) approach.A 3D magnetization transfer (MT) sequence was acquired using a scan-rescan imaging protocol in nine healthy volunteers. VOI definition masks for the MTR measurements were generated using FreeSurfer and compared to a manual region of interest (ROI) approach. (The longitudinal stability of MTR was monitored using agar gel phantom over a 5-month period.) Intraclass correlation coefficients (ICCs), coefficients of variation (CVs), and instrumental standard deviation (ISD) were determined.CVs ranged from 1.29%-2.64% (automated) vs. 1.30%-3.40% (manual). ISDs ranged from 0.62-1.10 pu (automated) vs. 0.68-1.67 pu (manual). The SD of the running difference was 1.70% for the phantom scans. The Bland-Altman method indicated interchangeability of the automated VOI and manual ROI measurements.The automated VOI approach for MTR measurement yielded higher ICCs, lower CVs, and lower ISDs compared to the manual method, supporting the utility of this strategy. These results demonstrate the feasibility of obtaining reliable MTR measurements in hippocampus and other critical subcortical regions.

Bland–Altman analysis is used to compare two different methods of measurement and to determine whether a new method of measurement may replace an existing accepted ‘gold standard’ method. In this work, Bland–Altman analysis has been applied to radiation dosimetry to compare the PTW Markus and Roos parallel plate ionisation chambers and a PTW PinPoint chamber against a Farmer type ionisation chamber which is accepted as the gold standard for radiation dosimetry in the clinic. Depth doses for low energy x-rays beams with energies of 50, 75 and 100 kVp were measured using each of the ionisation chambers. Depth doses were also calculated by interpolation of the data in the British Journal of Radiology (BJR) Report 25. From the Bland–Altman analysis, the mean dose difference between the two parallel plate chambers and the Farmer chambers was 1% over the range of depths measured. The PinPoint chamber gave significant dose differences compared to the Farmer chamber. There were also differences of up to 12% between the BJR Report 25 depth doses and the measured data. For the Bland–Altman plots, the lines representing the limits of agreement were selected to be a particular percentage agreement e.g. 1 or 2%, instead of being based on the standard deviation ( σ ) of the differences. The Bland–Altman statistical analysis is a powerful tool for making comparisons of ionisation chambers with an ionisation chamber that has been accepted as a ‘gold standard’. Therefore we conclude that Bland–Altman analysis does have a role in assessing radiation dosimeter performance relative to an established standard.

Purpose The application of manganese-enhanced MRI (MEMRI) to measure retinal function in humans is unclear. To begin to address this gap, we tested the hypothesis that an FDA-approved manganese-based MRI contrast agent, Teslascan, is useful for measuring functional intraretinal ionic regulation. Methods Anesthetized dark- or light-adapted male healthy Sprague–Dawley rats were infused for 30 min with 10 μmol/kg of Teslascan (clinically relevant dose; n = 5), 100 μmol/kg Teslascan ( n = 5), or saline ( n = 5). Four hours post-administration, high resolution MEMRI data were collected. Intraretinal signal intensities and enhancements were measured. Modelling was performed to estimate apparent retinal transfer constant K i and to determine optimal data acquisition parameters. Results In light-adapted rats, intraretinal enhancements responded in a dose–response manner. In addition, in the outer retina the effect of light-adaptation was to reduce significantly Mn 2+ uptake and K i compared to dark-adaptation. A non-significant change was also observed in the inner retina. Modelling shows Mn 2+ plasma concentration reaching a plateau after about 2 h. Apparent K i values for the clinically relevant dose are 3–6 × 10 −3 min −1 , decreasing to 0.5–0.6 × 10 −3 min −1 at the higher dose. Intraretinal signal is almost linear with K i . Optimal TR for a spin-echo sequence is 0.4–1.4 s. Conclusion First time evidence is presented that a clinically relevant dose and route of Teslascan can be used to measure intraretinal function. The potential for future clinical application of MEMRI in a broad range of retinopathies is high.

Adult low-grade gliomas (LGG) grow slowly, but most eventually undergo malignant transformation. The relationship between tumour volume, growth rate and the likelihood of transformation is unknown. Twenty-seven patients with biopsy-proven, untreated LGG had at least three MRI studies at 6 monthly intervals. Tumour volumes and growth rates were calculated using semi-automated segmentation, and analysed in a hierarchical regression model. In a 3-year period, patients who showed clinical deterioration and/or new (or significantly increased) contrast enhancement were classified as transformers (T), whilst non-transformers (NT) remained stable clinically and by conventional radiological criteria. All LGG showed progressive growth. Volumes at study entry were smaller in 9NT (57 ml, 95% CI 35-80 ml) than in 18T (83 ml, 95% CI 70-96 ml) (p=0.03). Average annual growth rates were lower in NT (16% (95% CI 9-23%)) than in T (26% (95% CI 20-31%)) (p=0.046), until the penultimate study. Growth in T increased to 56% p.a. (95% CI 20-92%) in the 6 months prior to transformation. In T, tumour volume was the most significant predictor of transformation in the following 12 months. Sequential measurement of LGG volume allows accurate determination of growth rates and identification of patients whose tumours are at high risk of early transformation.

There is increasing interest in imaging cadavers for noninvasive autopsies for research purposes. However, the temperature is well below that of in vivo imaging, and a variety of interesting 'cold brain' effects are observed. At lower temperatures conventional FLAIR sequences no longer produce dark cerebrospinal fluid (CSF); T(1) is reduced from about 4.0 sec in vivo to 1.7 sec at 1 degrees C. The diffusion coefficient (DC) of CSF is much reduced (from 3.1 10(-9) m(2)s(-1) in vivo to 1.1 at 1 degrees C). DC values therefore provide a noninvasive thermometer to measure brain core temperature to within 1.0 degrees C. In three cadavers DC values were 1.1-1.5 10(-9) m(2)s(-1), indicating brain core temperatures of 1-10 degrees C, consistent with external thermocouple measurements. An improved inversion time (TI(0)) can then be found for FLAIR. At 10 degrees C this Cold FLAIR sequence (TI(0) = 1.5 sec) gave black CSF. Expressions for CSF DC and T(1) as a function of temperature were produced. A measurement of CSF DC could be converted directly to temperature and the required TI(0) found. In vitro values of CSF DC were about 1% lower than that of water. Thus, FLAIR imaging can be optimized for cadaveric brains at low and unknown temperatures, thereby improving value for autopsy purposes and facilitating comparisons with in vivo imaging.

PURPOSE: To prospectively measure magnetization transfer (MT) parameters, along with established atrophy parameters, in patients with Alzheimer disease (AD) and in age- and sex-matched control subjects. MATERIALS AND METHODS: Participants provided informed consent, and additional assent was obtained from next of kin of all patients with AD. The study was approved by the local ethics committee. Fourteen patients with AD (seven men; mean age, 67.2 years+/-6.5 [standard deviation]) and 14 control subjects (nine men; mean age, 65.5 years+/-9.4) underwent volumetric T1-weighted magnetic resonance and MT imaging. Whole-brain and total hippocampal volumes were adjusted for total intracranial volume. MT images were processed to derive four fundamental parameters in the hippocampal region by using the two-pool model of the MT phenomenon. Pearson correlation coefficients were used to assess the association between volumetric and MT parameters and Mini-Mental State Examination (MMSE) results. Logistic regression models were used to investigate whether combinations of parameters associated with MMSE could help provide better group discrimination. RESULTS: Patients with AD had significantly reduced whole-brain (P=.001) and total hippocampal (P

MULTIPLE SCLEROSIS (MS) IS CHARACTERIZED by chronic inflammation and demyelination of the central nervous system. Magnetic resonance (MR) techniques are widely used to monitor the course of patients with MS. T2-weighted and gadolinium (Gd)-enhanced T1-weighted MR images display MS white matter lesions (WMLs) with high sensitivity and are useful in diagnosis (1,2). However, these MR measures correlate only modestly with disability (3,4), in part because—apart from a relationship between inflammation and Gd enhancement (5,6)—they do not distinguish key pathological features of MS, such as demyelination, remyelination, axonal loss, and gliosis (7). Additional MR measures have been developed that are quantitative and potentially more pathologically specific. These include volumetric measurements, magnetization transfer (MT) imaging, quantitative T1- and T2-relaxation time (RT) measurements, diffusion, and MR spectroscopic (MRS) metabolite concentrations (8). Investigation of postmortem tissue allows direct assessment of the relationship between quantitative MR (qMR) measures and their pathological substrates. So far such studies have been performed to investigate the pathological correlates of T1-hypointensity (9,10), T1-RT (11), transverse magnetization decay (also known as multiexponential T2-RT) (12), and MT ratio (MTR) (10,11,13). The MTR reflects the exchange of magnetization between protons in (at least) two pools: those that are freely mobile (conventionally referred to as the “A pool”), and those that are associated with macromolecules, such as in myelin or axonal membranes (the “B pool”) (14,15). Recent studies have suggested MTR as a putative marker of myelin content in postmortem MS brain and, by inference, in patients with MS in vivo (11,13). However, studies using animal models of demyelination have suggested that MTR may also be influenced by 1) other tissue properties, including inflammation (16,17), concentrations, and the RTs of the different proton pools; and 2) sequence-dependent factors, such as the frequency of the saturation pulse (18-20). A more detailed description of the MT effect can be achieved by extracting fundamental indices of MT, such as the fraction of macromolecular protons (fB) (21-23). As these quantitative MT (qMT) indices are absolute measures, they may also be independent of the MR system used, making comparisons between studies involving different sites and MR systems more straightforward (14). Promising results of in vivo studies in patients with MS (22,24-27) prompted us to assess in postmortem MS brain the association of two qMT indices, fB and T2-RT of the macromolecular proton pool (T2B), with myelin content, axonal count, and gliosis. MTR and T1-RT were acquired from the same brain specimens, thereby significantly extending a previously reported dataset (11).

RF field B1 nonuniformity is the largest cause of error in the quantitative measurement of many clinically relevant parameters in MR images and spectra. Knowledge of the absolute flip angles at every region will improve the accuracy and precision of such parameters. This method uses the 180 degrees signal null to construct a flip angle map of the entire brain in less than 4 min, independent of T1, T2, and proton density. Three spoiled gradient echo volume acquisitions of the whole brain were made with three different flip angles. The optimum choice of flip angles was determined to be 145 degrees, 180 degrees, and 215 degrees. Linear regression analysis was used to determine the nominal (system calibrated) flip angle required for a signal null at every pixel and thence determine the absolute flip angle at that location. The experiment utilizes an existing MR sequence supplied by the scanner manufacturer. The technique is validated experimentally and a theoretical investigation into the optimum experimental parameters is presented.

OBJECT: 1. Identify sources of variation affecting Magnetisation Transfer Ratio (MTR) histogram reproducibility between-centres. 2. Demonstrate complete elimination of inter-centre difference.MATERIALS AND METHODS: Six principle sources of variation were summarised and analysed. These are: the imager coil used for radiofrequency (RF) transmission, imager stability, the shape and other parameters describing the Magnetisation Transfer (MT) pulse, the MT sequence used (including its parameters), the image segmentation methodology, and the histogram generation technique. Transmit field nonuniformity and B1 errors are often the largest factors. PLUMB (Peak Location Uniformity in MTR histograms of the Brain) plots are a convenient way of visualising differences. Five multi-centres studies were undertaken to investigate and minimise differences.RESULTS: Transmission using a body coil, with a close-fitting array of surface coils for reception, gave the best uniformity. Differences between two centres, having MR imagers from different manufacturers, were completely eliminated by using body coil excitation, making a small adjustment to the MT pulse flip angle, and carrying out segmentation at a single centre. Histograms and their peak location and height values were indistinguishable.CONCLUSIONS: Body coil excitation is preferred for multi-centre studies. Analysis (segmentation and histogram generation) should ideally be carried out at a single site.

Segmentation of diffusion-weighted echo-planar imaging (DW-EPI) is challenging because of concerns regarding spatial resolution and distortion. Methods commonly used require manual input and often need thresholding measures to segment white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). This may introduce operator bias and misclassification error. When comparing patients with a diffuse disease process-such as multiple sclerosis (MS)--with healthy controls, although information from all images may be biased due to disease effect, this is more so if the data set employed to perform segmentation is also used as a measured outcome for the study, for example, fractional anisotropy maps. Presented in this work is an unbiased method for segmenting DW-EPI data sets using the b=0 and single-shot inversion recovery EPI into WM, GM and CSF. The method employs an iterative clustering technique to account for partial volume effects and signal variation caused by radiofrequency inhomogeneity. The technique is evaluated with both real and synthetic brain data and results compared with statistical parametric mapping (SPM02). With synthetic brain data, where a gold standard of segmentation exists, the presented method showed less misclassification compared to SPM02. The unbiased method proposed may provide a more accurate methodology of segmentation in the analysis of DWI-EPI images in conditions such as MS.

There are currently four problems in characterising small nonuniform lesions or other objects in Magnetic Resonance images where partial volume effects are significant. Object size is over- or under-estimated; boundaries are often not reproducible; mean object value cannot be measured; and fuzzy borders cannot be accommodated. A new measure, Object Strength, is proposed. This is the sum of all abnormal intensities, above a uniform background value. For a uniform object, this is simply the product of the increase in intensity and the size of the object. Biologically, this could be at least as relevant as existing measures of size or mean intensity. We hypothesise that Object Strength will perform better than traditional area measurements in characterising small objects. In a pilot study, the reproducibility of object strength measurements was investigated using MR images of small multiple sclerosis (MS) lesions. In addition, accuracy was investigated using artificial lesions of known volume (0.3-6.2 ml) and realistic appearance. Reproducibility approached that of area measurements (in 33/90 lesion reports the difference between repeats was less than for area measurements). Total lesion volume was accurate to 0.2%. In conclusion, Object Strength has potential for improved characterisation of small lesions and objects in imaging and possibly spectroscopy.

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.\ud \ud \ud

Abnormalities within normal-appearing grey and white matter (NAGM and NAWM) occur early in the clinical course of multiple sclerosis (MS) and can be detected in-vivo using the magnetisation transfer ratio (MTR). To better characterize the rates of change in both tissues and to ascertain when such changes begin, we serially studied a cohort of minimally disabled, early relapsing-remitting MS patients, using NAGM and NAWM MTR histograms. Twenty-three patients with clinically definite early relapsing-remitting MS (mean disease duration at baseline 1.9 years), and 19 healthy controls were studied. A magnetisation transfer imaging sequence was acquired yearly for two years. Twenty-one patients and 10 controls completed followup. NAWM and NAGM MTR histograms were derived and mean MTR calculated. A hierarchical regression analysis, adjusting for brain parenchymal fraction,was used to assess MTR change over time. MS NAWM and NAGM MTR were significantly reduced in comparison with controls at baseline and, in patients, both measures decreased further during follow-up: (-0.10 pu/year, p=0.001 and -0.18 pu/year, p

Dynamic, contrast-enhanced MRI (deMRI) is increasingly being used to evaluate cerebral microcirculation. There are two different approaches for analyzing deMRI data. Intravascular indicator dilution theory has been used to estimate blood volume (and perfusion), usually from T(2)- or T(2) (*)-weighted images of the first pass of the bolus. However, the theory assumes that the tracer (i.e., contrast agent) remains intravascular, which is often not the case when the blood-brain barrier (BBB) is damaged. Furthermore, the method provides no information on the vascular transfer constant. Pharmacokinetic modeling analyses of T(1)-weighted images after first pass do give values of the vascular transfer constant and the volume of the extravascular, extracellular space (EES), but they generally are unable to give estimates of blood volume. In this study we apply pharmacokinetic modeling to dynamic T(2) (*)-weighted imaging of the first pass of a tracer bolus. This method, which we call first-pass pharmacokinetic modeling (FPPM), gives an estimate of the blood volume, vascular transfer constant, and EES volume. The method was applied to a group of 26 patients with surgically proven tumors (10 glioblastomas multiforme (GBMs), six lymphomas, and 10 meningiomas). The measurements of the blood volume and transfer constant were consistent with the known physiology of these tumors.

The aim of this study was to assess the effect of differences in acquisition technique on whole-brain apparent diffusion coefficient (ADC) histogram parameters, as well as to assess scan-rescan reproducibility. Diffusion-weighted imaging (DWI) was performed in 7 healthy subjects with b-values 0-800, 0-1000, and 0-1500 s/mm(2) and fluid-attenuated inversion recovery (FLAIR) DWI with b-values 0-1000 s/mm(2). All sequences were repeated with and without repositioning. The peak location, peak height, and mean ADC of the ADC histograms and mean ADC of a region of interest (ROI) in the white matter were compared using paired-sample t tests. Scan-rescan reproducibility was assessed using paired-sample t tests, and repeatability coefficients were reported. With increasing maximum b-values, ADC histograms shifted to lower values, with an increase in peak height ( p0.01). With FLAIR DWI, the ADC histogram shifted to lower values with a significantly higher, narrower peak ( p0.01), although the ROI mean ADC showed no significant differences. For scan-rescan reproducibility, no significant differences were observed. Different DWI pulse sequences give rise to different ADC histograms. With a given pulse sequence, however, ADC histogram analysis is a robust and reproducible technique. Using FLAIR DWI, the partial-voluming effect of cerebrospinal fluid, and thus its confounding effect on histogram analyses, can be reduced.

A novel method is presented for the removal of spikes, caused by the division of two series of integers, from high-resolution histograms. When two series of integers are divided the results take the form of a nonuniform distribution. Such a division is often used in medical imaging, due to the storage of most images as integers. An example of this is the division of the saturated and unsaturated signal intensities to obtain a magnetization transfer ratio. Histograms produced using these methods often contain spikes relating to the nonuniform distribution mentioned above. These spikes can have serious implications for certain histogram characteristics. Most commonly, peak height and location can be seriously distorted by these spikes, which have predictable locations. These spikes can be removed by the addition of uniformly distributed noise to the integer signal intensities before division.

Quantitative analysis of magnetization transfer images has the potential to allow a more thorough characterization of the protons, both bound and free, in a tissue by extracting a number of parameters relating to the NMR properties of the protons and their local environment. This work develops previously presented techniques to produce estimates of parameters such as the bound proton fraction, f, and the transverse relaxation time of the bound pool, T(2B), for the whole brain in a clinically acceptable imaging time. This is achieved by limiting the number of data collected (typically to 10); to collect 28 5-mm slices with a reconstructed resolution of 0.94 x 0.94 mm. The protocol takes 82 sec per data point. The fitting technique is assessed against previous work and for fitting failures. Maps and analysis are presented from a group of seven controls and 20 multiple sclerosis patients. The maps show that the parameters are sensitive to tissue-specific differences and can detect pathological change within lesions. Statistically significant differences in parameters such as T(2B) and f are seen between normal-appearing white matter, multiple sclerosis lesions, and control white matter. Whole-brain histograms of these parameters are also presented, showing differences between patients and controls.

Background: In 10–15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. Methods: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75 % probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). Results: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = −0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = −0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. Conclusions: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

To the editor: Using orally administered deuterium-labeled water to label neutrophils in vivo, Pillay et al measured urinary and blood deuterium-to-proton enrichment ratios at intervals of ∼ 12 days over several weeks before and after termination of intake.[1][1] From mathematical modeling they

The mean apparent diffusion coefficient (ADC) of the human optic nerve (ON) has been quantified in vivo, and mean ADC maps are shown along the complete length of the nerve from the globe to the optic chiasm. The mean ADC, over the whole nerve, is shown to be 1058 x 10(-6) mm(2) s(-1) (standard deviation (SD), over nine 3-mm slices, 101x10(-6) mm(2) s(-1); range (833-1178)x10(-6) mm(2) s(-1)). The robustness of the method relies on acquisition of high-resolution coronal images of the ON using the ZOOM-EPI technique, which makes use of a shortened echo train length for increased resolution with decreased susceptibility-induced distortions. Suppression of the cerebrospinal fluid (CSF) and fat signals from tissues that surround the ON also helps successful identification and delineation of the nerve. Averaging of magnitude images is used to compensate for the inherently low signal-to-noise ratio (SNR) of the acquired images; the effects of the Rayleigh distributed noise in such images are allowed for during ADC calculations.

Two simple methodologies for correcting the errors in T2 maps for phantom measurements are presented; they both give accurate MRI maps with a low coefficient of variation (CV). The rate correction method is based on an equation relating the true T2 (T2,t) and that determined experimentally (T2,exp) for homogenous phantoms. The response matrix method is a phenomenological analysis of the difference between T2,exp and T2,t, from which correction factors are computed for a range of T2 values and for every pixel of an image. The factors were obtained from phantoms filled with a homogeneous gelatin gel and having different T2,t values. The CV in homogeneous phantom measurements were reduced from 2.5-4.0% to approximately 0.6-2.0% for T2,t values ranging from 180-600 ms. Examples are shown for the correction of T2 maps of phantoms filled with polymer dosimeter gel irradiated with photon beams from a linear accelerator. The methodologies presented can easily be implemented on a clinical MRI scanner.

The retinal oxygenation response to a hyperoxic challenge measured using MRI appears to be an early and accurate marker of retinopathy risk in experimental models, with promising clinical potential. However, the application of this technique in humans is limited by blinking artifacts that can confound detection of subtle signal intensity changes. We asked subjects to refrain from blinking during a 12-s fast low-angle shot (FLASH) image, and to blink if needed during the following 3-s rest period. This no-blink blink cycle was repeated sequentially 20 times during either room-air or 100% oxygen breathing. Significant change (P < 0.05) was detected for the first time from the resultant blinking-artifact-free images in the preretinal vitreous oxygen tension (upper limit of about 13 mm Hg (1.8 KPa, N = 3)) following a 10-min hyperoxic inhalation challenge. These results provide the proof-of-concept data needed for future MRI evaluation of the retinal oxygenation response and human retinopathy, such as diabetic retinopathy.

A range of liquids suitable as quality control test objects for measuring the accuracy of clinical MRI diffusion sequences (both apparent diffusion coefficient and tensor) has been identified and characterized. The self-diffusion coefficients for 15 liquids (3 cyclic alkanes: cyclohexane to cyclooctane, 9 n-alkanes: n-octane to n-hexadecane, and 3 n-alcohols: ethanol to 1-propanol were measured at 15-30 degrees C using an NMR spectrometer. Values at 22 degrees C range from 0.36 to 2.2 10(-9) m(2)s(-1). Typical 95% confidence limits are +/-2%. Temperature coefficients are 1.7-3.2% degrees C. T1 and T2 values at 1.5 T and proton density are given. n-tridecane has a diffusion coefficient close to that of normal white matter. The longer n-alkanes may be useful T2 standards. Measurements from a spin-echo MRI sequence agreed to within 2%.

Navigator echoes provide a means with which to remove motion artifacts from diffusion-weighted images obtained using any multishot imaging technique. However, residual motion artifact is often present in the corrected images rendering the technique unreliable. It is shown that velocity-compensated diffusion sensitization when used in tandem with a navigator echo further reduces the degree of residual motion artifacts present in the corrected images and improves the reliability and clinical utility of the technique. This is demonstrated by applying a method for quantification of motion artifact to brain images of healthy volunteers scanned using both conventional (Stejskal-Tanner) and velocity-compensated gradient sensitization. Other factors affecting the efficacy of the navigator echo technique, such as brain pulsatile motion, gradient b factor, and navigator echo signal-to-noise ratio, are also discussed.

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is a method of imaging the physiology of the microcirculation. A series of recent clinical studies have shown that DCE MRI can measure and predict tumor response to therapy. Recent advances in MR technology provide the enhanced spatial and temporal resolution that allow the application of this methodology in the management of cancer patients. The September issue of this journal provided a microcirculation section to update readers on this exciting and challenging topic. Evidence is mounting that DCE MRI-based measures correlate well with tumor angiogenesis. DCE MRI has already been shown in several types of tumors to correlate well with traditional outcome measures, such as histopathologic studies, and with survival. These new measures are sensitive to tumor physiology and to the pharmacokinetics of the contrast agent in individual tumors. Moreover, they can present anatomical images of tumor microcirculation at excellent spatial resolution. Several issues have emerged from recent international workshops that must be addressed to move this methodology into routine clinical practice. First, is complex modeling of DCE MRI really necessary to answer clinical questions reliably? Clinical research has shown that, for tumors such as bone sarcomas, reliable outcome measures of tumor response to chemotherapy can be extracted from DCE MRI by methods ranging from simple measures of enhancement to pharmacokinetic models. However, the use of similar methods to answer a different question-the differentiation of malignant from benign breast tumors-has yielded contradictory results. Thus, no simple, one-size-fits-all-tumors solution has yet been identified. Second, what is the most rational and reliable data collection procedure for the DCE MRI evaluation? Several groups have addressed population variations in some key variables, such as tumor T(1)0 (T(1) prior to contrast administration) and the arterial input function C(a)(t) for contrast agent, and how they influence the precision and accuracy of DCE MRI outcomes. However, despite these potential complications, clinical studies in this section show that some tumor types can be assessed by relatively simple dynamic measures and analyses. The clinical scenario and tumor type may well determine the required complexity of the DCE MRI exam procedure and its analysis. Finally, we suggest that a consensus on naming conventions (nomenclature) is needed to facilitate comparison and analysis of the results of studies conducted at different centers. J. Magn. Reson. Imaging 10:903-907, 1999.

Knowledge of water diffusion characteristics within the human spinal cord may provide important information about the structural nature of spinal cord pathology. However, the sensitivity of diffusion imaging methods to motion and the requirement for high in-plane resolution has hitherto restricted study of spinal cord diffusion to excised samples. The first diffusion images of the human cervical spinal cord in vivo are presented using a navigated pulsed-gradient spin-echo sequence. Anisotropic diffusion in the cord is demonstrated in agreement with in vitro studies, and further development of the technique for clinical studies is discussed.

Pharmacokinetic analysis using dynamic magnetic resonance imaging provides insight into various physiological aspects of tumors, including capillary wall permeability and the volume of the interstitial space. This physiology may be investigated in either a heuristic or model-based fashion using various methods presented in the literature. This review describes many of these approaches and provides some guidelines for those intending to use dynamic magnetic resonance imaging in the investigation of neoplasms.

To assess the importance of intercenter variations when measuring magnetization transfer ratio (MTR) in the brain, six European centers measured MTR in normal white matter. MTR ranged from 9 to 51 percent units (25 sequences). The effective flip angle of the saturating pulse divided by the pulse repetition time (ENRsat degrees/msec) was a good predictor of MTR (MTR = 3.25 ENRsat).

Quantitative comparisons of abnormalities in MRI scans between patients or within patients serially are affected by variations in MR scanner performance. A histogram matching method is proposed to correct for variation in scanner sensitivity. It is demonstrated that this histogram matching method reduced the variation in white matter intensities across normal subjects from 7.5 to 2.5% and provided a method to remove the threshold dependency in lesion volume measurement with global thresholding in patients with multiple sclerosis (MS). The effectiveness of the method was compared with three other possible correction schemes. The histogram matching method was shown to be 2 to 5 times better.

The characteristics of transverse magnetisation decay of 120 longstanding lesions and 40 regions of normal-appearing white matter have been analysed in 40 patients with multiple sclerosis (MS) and 10 normal controls. Fifty lesions showed a biexponential decay in which two water compartments-one probably intracellular, the other extracellular-could be defined. There was a higher frequency of biexponential lesions in patients with a primary progressive course but no significant difference between benign and secondary progressive groups. Seventy lesions showed a monoexponential decay, of which 31 showed a T2 of greater than 200 ms, implying that these lesions were predominantly composed of extracellular rather than intracellular water. The results imply that an expanded extracellular space within chronic MS brain lesions is a common finding at all levels of disability and disease course. In so far as an expanded extracellular space implies axonal loss, the results suggest that the latter occurs commonly in longstanding MS lesions. The lack of correlation with disability suggests a limited role for the technique in therapeutic monitoring.

The selection of a suitable low dielectric constant liquid for radiofrequency coil nonuniformity measurements is described. Measurements of dielectric constant (relative permittivity) were made on a range of candidate liquids. After excluding liquids that were too inflammable or too viscous, Esso Bayol 82 oil (dielectric constant epsilon' = 2.37) was chosen. At 1.5 T, a 27 cm diameter cylindrical phantom (test object) filled with Bayol 82 has a maximum nonuniformity of 1.9% arising from radiofrequency standing waves. The maximum diameter cylinder that can be used without the nonuniformity exceeding 2% is given for a range of liquids and field strengths. The construction of customized containers that fit closely inside a radiofrequency head coil from glass fiber reinforced resin ("fiberglass") is described. Thermal expansion of the liquid takes place without a rise in the internal pressure in the container.

Nicotine has been shown to speed attentional reorienting in cued target detection tasks, and work in young adults suggest that individuals carrying the apolipoprotein E (APOE) e4 allele might show greater sensitivity to the cognitive effects of nicotine. The APOE e4 allele is associated with increased risk of Alzheimer’s disease (AD), and increased sensitivity to nicotine might reflect early cholinergic differences that relate to an enhanced risk of AD. The aim of this study was to investigate effects of nicotine and APOE on attentional reorienting in mid-age participants. APOE e4 (e4+) were compared to non-APOE e4 (e4–) carriers, and functional magnetic resonance imaging (fMRI) data acquired. Neural data showed that nicotine effects, and the network involved in reorienting, was consistent with studies in young adults. Nicotine improved attentional reorienting at the trend level. Although there were no behavioural effects of genotype, genotype effects were present neurally: e4+ showed decreased extrastriate activation, and enhanced effects of nicotine on reorienting in right middle frontal regions. Drug by genotype interactions were present in hippocampal and anterior cingulate regions. These results are consistent with differential sensitivity to nicotine according to APOE status, possibly reflecting abnormal cholinergic function and accelerated cognitive ageing in mid-age e4+.

4,764 subjects, and 4,779 MR Imaging Sessions searchable across six projects to promote re-use and integration of these valuable shared data. The NITRC-CE provides simplified deployment of cloud-based computation that supports FreeSurfer, FSL, AFNI and many other software resources applicable to AD research.Conclusions: In summary, NITRC is now an established knowledge environment for the neuroimaging community where tools and resources are presented in a coherent and synergistic environment. We encourage the dementia research community to continue providing design and content feedback and to utilize these resources in support of data sharing requirements, software dissemination and cost-effective computational performance.

Introduction There are increasing opportunities to use dynamic contrast-enhanced (DCE) T 1 -weighted imaging to characterize tumor and other pathological biology and treatment response, using modern fast sequences that can provide good temporal and spatial resolution combined with good organ coverage [1]. Quantification in MRI is recognized as an important approach to characterize tissue biology. This chapter provides an introduction to the physical concepts of mathematical modeling, image acquisition, and image analysis needed to measure aspects of tissue biology using DCE imaging, in a way that should be accessible for a research-minded clinician. Quantification in MRI represents a paradigm shift, a new way of thinking about imaging [2]. In qualitative studies, the scanner is a highly sophisticated camera, collecting images that are viewed by an experienced radiologist. In quantitative studies, the scanner is used as a sophisticated measuring device, a scientific instrument able to measure many properties of each tissue voxel (e.g., T 1 , T 2 , diffusion tensor,magnetization transfer, metabolite concentration, K trans ). An everyday example of quantification would be the bathroom scales, used to measure our weight. We expect that the machine output shown on the dial, in kg, will be accurate (i.e., close to the true value), reproducible (i.e., if we make repeated measurements over a short time they will not vary), reliable (the scales always work), and biologically relevant (the quantity of weight does indeed relate to our health). An example of a clinical measurement would be a blood test; we expect it to work reliably every time. This is the aspiration for quantitative MRI: that it should deliver a high-quality measurement that relates only to the patient biology (and not the state of the scanner at the time of measurement).